通过低温电子显微镜单粒子分析和低温电子断层扫描，课题组研究人员将流感RNP定义为一个右旋的反平行双螺旋结构，病毒RNA被封装在小槽中。单个核蛋白亚基通过一个灵活的尾环连接起来，该尾环插入邻近的保守口袋中。该团队可视化了不同功能状态下RNP中的病毒聚合酶，揭示了它如何通过链滑动来访问RNA模板，同时保持RNP的双螺旋结构。针对尾环结合界面，研究小组确定了作为潜在抗流感抑制剂的先导化合物。这些发现阐明了支持流感病毒复制的分子决定因素，并强调了抗病毒药物开发的一个有希望的靶点。
据介绍，流感病毒主题在保守核糖核蛋白（RNP）复合体的背景下复制和转录其基因组。
附：英文原文
Title: Molecular basis of influenza ribonucleoprotein complex assembly and processive RNA synthesis
Author: Ruchao Peng, Xin Xu, Binod Nepal, Yikang Gong, Fenglin Li, Max B. Ferretti, Mingyang Zhou, Kristen W. Lynch, George M. Burslem, Sandhya Kortagere, Ronen Marmorstein, Yi-Wei Chang
Issue&Volume: 2025-05-15
Abstract: Influenza viruses replicate and transcribe their genome in the context of a conserved ribonucleoprotein (RNP) complex. By integrating cryo–electron microscopy single-particle analysis and cryo–electron tomography, we define the influenza RNP as a right-handed, antiparallel double helix with the viral RNA encapsidated in the minor groove. Individual nucleoprotein subunits are connected by a flexible tail loop that inserts into a conserved pocket in its neighbor. We visualize the viral polymerase in RNP at different functional states, revealing how it accesses the RNA template while maintaining the double-helical architecture of RNP by strand sliding. Targeting the tail loop binding interface, we identify lead compounds as potential anti-influenza inhibitors. These findings elucidate the molecular determinants underpinning influenza virus replication and highlight a promising target for antiviral development.
DOI: adq7597
Source: https://www.science.org/doi/10.1126/science.adq7597